Various oligopeptide derivatives have demonstrated various medicinal uses, such as enzyme inhibitors as disclosed in U.S. Pat. No. 4,483,850. It is also known that various oligopeptides have anti-tumor activity as disclosed in U.S. Pat. Nos. 4,216,208 and 4,314,999. Antibiotic activity of oligopeptides is disclosed in U.S. Pat. No. 4,454,065. Naturally occurring oligopeptides, netropsin and distamycin, have been discovered as having antiviral and anti-tumor activity. The chemical formulas for netropsin and distamycin are as follows: ##STR2##
These oligopeptides are disclosed in Julia, M., Preau-Joseph, N., C. R. Hebd-Seances, Acad. Sci. 1963, 257. 1115 and Arcamone, F.; Orezzi, P. G.; Barbier, W.; Nicolella, V.; Penco, S.; Gazz. Chim. Ital., 1967, 97, 1097.
Netropsin and distamycin contain pyrrole moieties connected by peptide bonds and with side chains, at least one of which is positively charged; i.e., an amidine group, or a group of the guanidyl type.
Only distamycin has been used as a therapeutic agent as commercialized and sold under the trade mark STALLIMYCIN HYDROCHLORIDE in the form of a 1% cream, ointment or paste. This composition has been used in the treatments of infections produced by herpes simplex, herpes zoster and vaccinia viruses. Topical application of distamycin has been limited due to its high cytotoxicity and a low therapeutic index which in the instance of treating the herpes virus is about 3.
U.S. Pat. No. 4,912,199 discloses oligopeptides containing pyrrole moieties which demonstrated significantly enhanced antiviral and anticancer activities as compared to the oligopeptides of the prior art.
According to this invention oligopeptides have been developed which have significantly enhanced antiretroviral activity compared to prior types of oligopeptides.